SSADH
MCID: SCC001
MIFTS: 51

Succinic Semialdehyde Dehydrogenase Deficiency (SSADH) malady

Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases categories
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Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetics Home Reference:21 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards based summary: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to wagr syndrome and obesity, and has symptoms including ataxia/incoordination/trouble of the equilibrium, hypotonia and intellectual deficit/mental/psychomotor retardation/learning disability. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (aldehyde dehydrogenase 5 family, member A1), and among its related pathways are Arginine and proline metabolism and Neurotransmitter Release Cycle. The compounds Succinic acid semialdehyde and vigabatrin have been mentioned in the context of this disorder. Affiliated tissues include eye, brain and liver.

Disease Ontology:8 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:42 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

Wikipedia:65 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

Description from OMIM:46 271980

GeneReviews summary for ssadh

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

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Succinic Semialdehyde Dehydrogenase Deficiency, Aliases & Descriptions:

Name: Succinic Semialdehyde Dehydrogenase Deficiency 8 9 19 42 21 46 10 48 62
4-Hydroxybutyric Aciduria 8 19 42 21 48
Gamma-Hydroxybutyric Aciduria 8 19 21
Ssadh Deficiency 19 42 21
Succinic Semialdehyde Dehydrogenase 9 20
 
4-Hydroxybutyricaciduria 21 62
Gamma-Hydroxybutyric Acidemia 21
Gamma-Hydroxybutyricaciduria 42
Gaba Metabolic Defect 42
Ssadh 8


Classifications:



Characteristics (Orphanet epidemiological data):

48
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood


External Ids:

Disease Ontology8 DOID:0060175
ICD10 via Orphanet26 E72.8
OMIM46 271980

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

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Diseases related to Succinic Semialdehyde Dehydrogenase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 16)
idRelated DiseaseScoreTop Affiliating Genes
1wagr syndrome31.0WT1
2obesity10.4
3neuroleptic malignant syndrome10.4
4juvenile absence epilepsy10.4
5canavan disease10.4
6dystonia10.4
7sleep disorder10.4
8mental retardation10.4
9hypotonia10.4
10status epilepticus10.4
11idiopathic generalized epilepsy10.4
12williams syndrome10.3
13dysequilibrium syndrome10.3
14d-2-hydroxyglutaric aciduria10.1
15cerebritis10.1
16homocarnosinosis9.9ABAT, ALDH5A1

Graphical network of diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Symptoms for Succinic Semialdehyde Dehydrogenase Deficiency

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Symptoms by clinical synopsis from OMIM:

271980

Clinical features from OMIM:

271980

Symptoms:

48 (show all 7)
  • ataxia/incoordination/trouble of the equilibrium
  • hypotonia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • organic acid metabolism anomalies
  • autosomal recessive inheritance
  • seizures/epilepsy/absences/spasms/status epilepticus
  • psychic/behavioural troubles

HPO human phenotypes related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show all 30)
id Description Frequency HPO Source Accession
1 muscular hypotonia hallmark (90%) HP:0001252
2 incoordination hallmark (90%) HP:0002311
3 cognitive impairment hallmark (90%) HP:0100543
4 behavioral abnormality typical (50%) HP:0000708
5 seizures typical (50%) HP:0001250
6 autosomal recessive inheritance HP:0000007
7 abnormality of eye movement HP:0000496
8 psychosis HP:0000709
9 autism HP:0000717
10 aggressive behavior HP:0000718
11 hallucinations HP:0000738
12 anxiety HP:0000739
13 delayed speech and language development HP:0000750
14 hyperactivity HP:0000752
15 intellectual disability HP:0001249
16 ataxia HP:0001251
17 muscular hypotonia HP:0001252
18 global developmental delay HP:0001263
19 hyporeflexia HP:0001265
20 motor delay HP:0001270
21 abnormality of metabolism/homeostasis HP:0001939
22 generalized tonic-clonic seizures HP:0002069
23 absence seizures HP:0002121
24 generalized myoclonic seizures HP:0002123
25 status epilepticus HP:0002133
26 eeg abnormality HP:0002353
27 hyperkinesis HP:0002487
28 infantile onset HP:0003593
29 phenotypic variability HP:0003812
30 self-injurious behavior HP:0100716

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

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Drug clinical trials:

Search ClinicalTrials for Succinic Semialdehyde Dehydrogenase Deficiency

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinic Semialdehyde Dehydrogenase Deficiency20 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

32
Eye, Brain, Liver, Globus pallidus

Animal Models for Succinic Semialdehyde Dehydrogenase Deficiency or affiliated genes

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Publications for Succinic Semialdehyde Dehydrogenase Deficiency

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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 64)
idTitleAuthorsYear
1
Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype. (25122112)
2014
2
A Novel Mutation of ALDH5A1 Gene Associated With Succinic Semialdehyde Dehydrogenase Deficiency. (25246302)
2014
3
Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semialdehyde dehydrogenase deficiency]. (23926001)
2013
4
Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency. (23430529)
2013
5
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
6
Succinic semialdehyde dehydrogenase deficiency: an inheritable neurometabolic disease]. (23516105)
2013
7
A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. (23825041)
2013
8
Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. (23430864)
2012
9
A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. (22437753)
2012
10
Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (21664777)
2011
11
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
12
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
13
Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report. (19896403)
2010
14
Head bobbing due to succinic semialdehyde dehydrogenase deficiency. (20548048)
2010
15
Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin]. (20018576)
2010
16
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
17
Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. (19172412)
2009
18
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
19
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
20
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
21
Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity. (16545979)
2006
22
Succinic semialdehyde dehydrogenase deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. (16542398)
2006
23
Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. (15582027)
2004
24
Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. (15093183)
2004
25
Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency. (15037717)
2004
26
Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency. (12829002)
2003
27
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. (12743223)
2003
28
Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. (12891656)
2003
29
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
30
Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography-mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency. (12127325)
2002
31
Selective involvement of the globus pallidus and dentate nucleus in succinic semialdehyde dehydrogenase deficiency. (12136353)
2002
32
Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. (11819156)
2002
33
A unique mouse model for succinic semialdehyde dehydrogenase deficiency with implications for gamma hydroxybutyrate intoxication. (11990378)
2002
34
MRI findings in succinic semialdehyde dehydrogenase deficiency. (10774997)
2000
35
Succinic semialdehyde dehydrogenase deficiency in siblings: clinical heterogeneity and response to early treatment. (10234622)
1999
36
Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9683595)
1998
37
The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients. (9093300)
1997
38
Succinic semialdehyde dehydrogenase deficiency: low excretion of metabolites in a neonate. (9061565)
1997
39
Differing clinical presentation of succinic semialdehyde dehydrogenase deficiency in adolescent siblings from Lifu Island, New Caledonia. (9266358)
1997
40
Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). (8803774)
1996
41
Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. (7564230)
1995
42
Pre- and postnatal diagnosis of succinic semialdehyde dehydrogenase deficiency using enzyme and metabolite assays. (7707697)
1994
43
Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) (8464836)
1993
44
Succinic Semialdehyde Dehydrogenase Deficiency (20301374)
1993
45
Succinic semialdehyde dehydrogenase deficiency associated with combined 4-hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. (2926573)
1989
46
Vigabatrin therapy in patient with succinic semialdehyde dehydrogenase deficiency. (2572834)
1989
47
Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. (3126356)
1987
48
Succinic semialdehyde dehydrogenase deficiency--a further case. (2433500)
1985
49
Succinic semialdehyde dehydrogenase deficiency. (6536727)
1984
50
Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. (6627675)
1983

Variations for Succinic Semialdehyde Dehydrogenase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

64 (show all 12)
id Symbol AA change Variation ID SNP ID
1ALDH5A1p.Cys93PheVAR_026199
2ALDH5A1p.Gly176ArgVAR_026200
3ALDH5A1p.Cys223TyrVAR_026201
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203
6ALDH5A1p.Gly268GluVAR_026204
7ALDH5A1p.Asn335LysVAR_026205
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210

Clinvar genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

6
id Gene Name Type Significance SNP ID Assembly Location
1ALDH5A1ALDH5A1, IVS9, G-T, +1single nucleotide variantPathogenic
2ALDH5A1ALDH5A1, IVS5, G-A, +1single nucleotide variantPathogenic
3ALDH5A1NM_170740.1(ALDH5A1): c.612G> A (p.Trp204Ter)single nucleotide variantPathogenicrs118203982GRCh37Chr 6, 24505099: 24505099
4ALDH5A1NM_170740.1(ALDH5A1): c.1273C> T (p.Arg425Ter)single nucleotide variantPathogenicrs118203983GRCh37Chr 6, 24528285: 24528285
5ALDH5A1NM_170740.1(ALDH5A1): c.1265G> A (p.Gly422Asp)single nucleotide variantPathogenicrs118203984GRCh37Chr 6, 24528277: 24528277
6ALDH5A1NG_008161.1: g.31299_33753deldeletionPathogenicGRCh37Chr 6, 24521495: 24523949

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Expression patterns in normal tissues for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
citrulline-nitric oxide cycle37
arginine degradation I (arginase pathway)37
proline degradation37
glutamine degradation I37
proline biosynthesis I37
superpathway of citrulline metabolism37
proline biosynthesis II (from arginine)37
citrulline biosynthesis37
arginine degradation VI (arginase 2 pathway)37
Urea cycle and metabolism of amino groups37
asparagine biosynthesis I37
4-hydroxyproline degradation I37
citrulline degradation37
9.5ALDH1B1, ALDH4A1
2
Show member pathways
9.5ALDH5A1, ABAT
3
Show member pathways
9.5ALDH5A1, ABAT
4
Show member pathways
aspartate biosynthesis37
9.5ALDH5A1, ABAT
59.0ALDH5A1, ALDH4A1, ABAT
6
Show member pathways
beta-alanine degradation I37
valine degradation I37
pyruvate fermentation to lactate37
isoleucine degradation I37
8.8ABAT, ALDH6A1, ALDH1B1
7
Show member pathways
phenylethylamine degradation I37
8.8ALDH1B1, ALDH6A1, ABAT
8
Show member pathways
8.0ABAT, ALDH6A1, ALDH4A1, ALDH5A1, ALDH1B1

Compounds for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Compounds related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 24)
idCompoundScoreTop Affiliating Genes
1Succinic acid semialdehyde249.8ALDH5A1, ABAT
2vigabatrin28 44 1111.8ABAT, ALDH5A1
3vitamin b6449.7ALDH5A1, ABAT
4Malonic semialdehyde249.7ALDH6A1, ABAT
5alpha-ketoglutarate449.7ALDH5A1, ABAT
62-Methyl-3-oxopropanoic acid249.6ALDH6A1, ABAT
7succinate449.6ABAT, ALDH5A1
8beta-alanine44 61 28 24 1113.6ALDH1B1, ABAT
9Gamma-Aminobutyric acid249.6ALDH1B1, ABAT
10famotidine44 2 24 1112.6ALDH4A1, ABAT
11valproic acid44 50 24 1112.5ALDH5A1, ABAT
12l-glutamic acid28 24 1111.5ALDH4A1, ABAT
13NADP249.5ALDH1B1, ALDH4A1
14succinic semialdehyde449.4ALDH5A1, AKR7A2, ABAT
15gamma-hydroxybutyrate449.4ABAT, AKR7A2, ALDH5A1
16taurine44 61 2411.3ABAT, WT1
17(S)-Methylmalonic acid semialdehyde249.2ALDH1B1, ALDH6A1, ABAT
18nadph44 2410.1ALDH1B1, ALDH4A1, ABAT
19ornithine44 2410.0WT1, ABAT
20Water249.0ALDH4A1, ALDH5A1, ALDH1B1
21nad28 249.9ALDH1B1, ALDH5A1, ALDH4A1, ALDH6A1
22nadh44 24 1110.9ALDH6A1, ALDH4A1, ALDH5A1, ALDH1B1
23glutamine448.9ABAT, ALDH5A1, WT1
24glutamate448.7ALDH5A1, ALDH4A1, ABAT

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrionGO:0057398.4ALDH1B1, ALDH5A1, ALDH6A1, ABAT
2mitochondrial matrixGO:0057597.7ALDH1B1, ALDH5A1, ALDH4A1, ALDH6A1, ABAT

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1neurotransmitter secretionGO:0072699.5ALDH5A1, ABAT
2gamma-aminobutyric acid catabolic processGO:0094509.4ALDH5A1, ABAT
3neurotransmitter catabolic processGO:0421359.2ALDH5A1, ABAT

Molecular functions related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1electron carrier activityGO:0090559.6ALDH4A1, AKR7A2
2aldehyde dehydrogenase (NAD) activityGO:0040299.2ALDH1B1, ALDH4A1

Products for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Sources for Succinic Semialdehyde Dehydrogenase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet